title: Relationship between 17-alpha hydroxyprogesterone caproate concentration and spontaneous preterm birth.
abstract: OBJECTIVE
  17-alpha hydroxyprogesterone caproate 250 mg weekly reduces recurrent spontaneous preterm birth in women with a prior spontaneous preterm birth by 33%. The dose is not based on pharmacologic considerations. A therapeutic concentration has not been determined hampering any attempt to optimize treatment. This study evaluated the relationship between 17-alpha hydroxyprogesterone caproate plasma concentrations and the rate of spontaneous preterm birth in women with singleton gestation.
  
  
  METHODS
  A single blood sample was obtained between 25 and 28 weeks' gestation from 315 women with a spontaneous preterm birth who participated in a placebo-controlled, prospective, randomized clinical trial evaluating the benefit of omega-3 supplementation in reducing preterm birth. All women in the parent study received 17-alpha hydroxyprogesterone caproate and 434 received omega-3 supplementation and 418 received a placebo. Plasma from 315 consenting women was analyzed for 17-alpha hydroxyprogesterone caproate concentration.
  
  
  RESULTS
  There were no differences between placebo and omega-3 supplemented groups in demographic variables, outcomes or in mean 17-alpha hydroxyprogesterone caproate concentration. Plasma concentrations of 17-alpha hydroxyprogesterone caproate ranged from 3.7-56 ng/mL. Women with plasma concentrations of 17-alpha hydroxyprogesterone caproate in the lowest quartile had a significantly higher risk of spontaneous preterm birth (P = .03) and delivered at significantly earlier gestational ages (P = .002) than did women in the second to fourth quartiles. The lowest preterm birth rates were seen when median 17-alpha hydroxyprogesterone caproate concentrations exceeded 6.4 ng/mL.
  
  
  CONCLUSIONS
  Low plasma 17-alpha hydroxyprogesterone caproate concentration is associated with an increased risk of spontaneous preterm birth. This finding validates efficacy of this treatment but suggests that additional studies are needed to determine the optimal dosage.
authors.affiliation: Department of Obstetrics and Gynecology and Reproductive Sciences and Pharmaceutical Sciences, University of Pittsburgh Schools of Medicine and Pharmacy, Pittsburgh, PA.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Caritis
authors.affiliation: Department of Obstetrics and Gynecology and Reproductive Sciences and Pharmaceutical Sciences, University of Pittsburgh Schools of Medicine and Pharmacy, Pittsburgh, PA.
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
authors.affiliation: The George Washington University Biostatistics Center, Washington, DC.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thom
authors.affiliation: Department of Obstetrics and Gynecology, Wake Forest University Health Sciences, Winston-Salem, and University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Margaret
authors.initials: M
authors.lastname: Harper
authors.affiliation: Maternal-Fetal Medicine Units, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Klebanoff
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Sorokin
authors.affiliation: Department of Obstetrics and Gynecology, Wake Forest University Health Sciences, Winston-Salem, and University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: John M
authors.initials: JM
authors.lastname: Thorp
authors.affiliation: Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, UT.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Varner
authors.affiliation: Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York, NY.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wapner
authors.affiliation: Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Iams
authors.affiliation: Department of Obstetrics and Gynecology, Women and Infants Hospital, Alpert Medical School, Brown University, Providence, RI.
authors.forename: Marshall W
authors.initials: MW
authors.lastname: Carpenter
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL.
authors.forename: William A
authors.initials: WA
authors.lastname: Grobman
authors.affiliation: Department of Obstetrics and Gynecology, Case Western Reserve University-MetroHealth Medical Center, Cleveland, OH.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Mercer
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Sciscione
authors.affiliation: Department of Obstetrics and Gynecology, University of Alabama at Birmingham School of Medicine, Birmingham, AL.
authors.forename: Dwight J
authors.initials: DJ
authors.lastname: Rouse
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Health Science Center at Houston, Houston, TX.
authors.forename: Susan
authors.initials: S
authors.lastname: Ramin
mesh_terms: D000077713:17 alpha-Hydroxyprogesterone Caproate; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006908:Hydroxyprogesterones / Q000008:administration & dosage / Q000097:blood*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood; D047928:Premature Birth / Q000097:blood* / Q000517:prevention & control; D012008:Recurrence
chemical_list: D015525:Fatty Acids, Omega-3; D006908:Hydroxyprogesterones; D000077713:17 alpha-Hydroxyprogesterone Caproate
keywords: 17-hydroxyprogesterone caproate concentration-response; dose response; pharmacodynamics